Critically ill patients usually present with circulatory hypoxemia and this is associated with a poorer prognosis. The aim of this experimental study was to examine the effect of U-74389G with specific regard to a hypoxemia/re-oxygenation protocol, on mean blood haemoglobin (Hgb) levels in rats.
Materials and methods: Forty rats (mean weight 231.9 g) were used in the study. Hgb levels were measured at sixty minutes (groups A and C) and at 120 minutes (groups B and D) of re-oxygenation. U-74389G was administered only in groups C and D.
Results: U-74389G administration non-significantly increased the Hgb levels by 3.95+2.10% (p=0.0604). Re-oxygenation time non-significantly increased the Hgb levels by 3.39+2.12% (p=0.1285). U-74389G administration and re-oxygenation time together, significantly increased the Hgb levels by 2.55%+1.25% (p=0.0423).
Conclusions: Results of this study indicate that U-74389G administration, re-oxygenation time, but mainly their interaction significantly increase the Hgb levels within the studied time limits.
Category Archives: issue
The Use of Novel Adopters for Acute Rib Fixation in Critical Chest Trauma, Undertaken by Orthopaedic Surgeons: an Observational Cohort Study
Background: Surgical stabilisation of acute rib fractures has recently undergone rapid change in the UK with respect to what type of injury is surgically stabilised and who undertakes the operation. This paper presents a review of the literature on surgical fixation and presents our early clinical experience using a recently introduced stabilising system.
Methods: Data was prospectively collected from the first 10 patients undergoing surgical stabilisation of acute rib fractures using the Synthes Matrix RIB plating system. The data included demographics, Injury Severity Score, length of stay in Intensive Care, length of time on a ventilator, analgesic requirements, pneumonia rates and mortality. Patients were followed up until they were discharged from hospital.
Results: Patients had an average Injury Severity Score of 26 (16-57), the average number of ribs fractured was 8.2 (4-14), nine patients had flail chest and one had multiple fractures, mean time from injury to fixation was 2.8 days. In the reported cohort, there were no deaths, two pneumonias (one had pneumonia on presentation). The average length of stay on a ventilator was three days and the average length of stay in Intensive Care was ten days.
Conclusion: The early results of this procedure are encouraging. We feel that the modern implants will provide superior results to the highly variable implants that have previously been used. Our results support the literature, showing that with this system, there is a decrease in mortality and morbidity and a decrease in the length of time on a ventilator and stay in Intensive Care.
New Targets for End-Stage Chronic Kidney Disease Therapy
Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors.
The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.
Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury
Traumatic Brain Injury (TBI) is one of the leading causes of death among critically ill patients from the Intensive Care Units (ICU). After primary traumatic injuries, secondary complications occur, which are responsible for the progressive degradation of the clinical status in this type of patients. These include severe inflammation, biochemical and physiological imbalances and disruption of the cellular functionality. The redox cellular potential is determined by the oxidant/antioxidant ratio. Redox potential is disturbed in case of TBI leading to oxidative stress (OS). A series of agression factors that accumulate after primary traumatic injuries lead to secondary lesions represented by brain ischemia and hypoxia, inflammatory and metabolic factors, coagulopathy, microvascular damage, neurotransmitter accumulation, blood-brain barrier disruption, excitotoxic damage, blood-spinal cord barrier damage, and mitochondrial dysfunctions. A cascade of pathophysiological events lead to accelerated production of free radicals (FR) that further sustain the OS. To minimize the OS and restore normal oxidant/antioxidant ratio, a series of antioxidant substances is recommended to be administrated (vitamin C, vitamin E, resveratrol, N-acetylcysteine). In this paper we present the biochemical and pathophysiological mechanism of action of FR in patients with TBI and the antioxidant therapy available.
Oxidative Stress in the Critically Ill Polytrauma Patient
The critically ill patient with primary multiple traumas and having secondary complications, presents a complex challenge to the trauma team. The most commonly encountered primary injuries are traumatic brain, spinal cord, pulmonary and abdominal injuries or trauma to the pelvis and the extremities. Moreover, severe inflammations, infections, hyper-metabolism, as well as biochemical and physiological imbalances, lead to a significant increase in morbidity and mortality.
Most recently, the role of free radicals has been a largely debated and reported topic. Once produced in excess, free radicals are responsible for inducing oxidative stress. The redox species known to have a destructive effect on cells include the superoxide anion, the hydroxyl radical, hydrogen peroxide, nitric oxide, peroxynitrite, lipid peroxyl and alkoxy lipid. Under normal conditions, free radicals are produced in the human body in small amounts, their activity being minimized by the body’s physiologically anti-oxidant systems which include superoxide dismutase, catalase, glutathione, glutathione peroxidase, peroxiredoxins, and glutaredoxins.
In the critically ill patient, severe physiological and biochemical imbalances significantly reduce the body’s anti-oxidant capacity, disrupting the redox balance [1]. A series of biomarkers are in use, designed to quantify oxidative stress. These comprise interleukin 1 beta, interleukin 6, interleukin 10, tumor necrosis alpha, components of the complement, plasmatic levels of antioxidant enzymes and the microRNA species [2]. [More]
Volume 1, Issue 3, July 2015
Fading Sugammadex, or Just Cautiously (re) Considered?!
Sugammadex, a synthetic cyclodextrin sodium salt, was heralded and initially marketed as the first selective relaxant binding agent (SRBA) designed to reverse rocuronium [1]. This chemically modified cyclodextrin basically swallowed rocuronium removing it from the effector site, which was a “paradigm shift” from the then current methodology [2]. Following the launch of rocuronium and the rapidly spreading practice of intubation on rocuronium in rapid sequence instead of succinylcholine, a need to reverse muscle relaxation in case of intubation failure emerged. Moreover, the well-known undesirables side effects of cholinesterase inhibitors needing blunting by coadministration of muscarinic antagonists enlarged the odds of experiencing unwanted extra drug effects [3]. Further studies supported the use of sugammadex to reverse a life-threatening situation defined as “cannot intubate, cannot ventilate” [4]. It was a genuine revolutionary approach [5].Thus sugammadex appeared as a rescue drug. It was then used as the best, the most rapid and the safest if not the single solution to reverse curarization, although controversies as to the standard ofrapid sequence induction and intubation[6] are going on [7]. The odds were favorable and still are if it were not for certain voices to say “nay” to sugammadex as a routine drug based mainly on cost related issues. [More]
Is therapeutic hypotermia viable in our region as a new option for sudden cardiac arrest caused by acute myocardial infarction?
To the editor of JCCM
Therapeutic hypothermia has become a widely accepted option for management of patients with cardiac arrest occurring in the setting of an Acute Myocardial Infarction [1]. Infarct size is one of the major determinants of future evolution of patients with myocardial infarction and every attempt should be made in order to reduce the amount of infarcted, necrotic myocardium. It has been suggested that induction of hypothermia before performing a percutaneous coronary intervention for urgent revascularisation might play a decisive role in reduction of infarct size [1]. In the same time, applying a mild cooling protocol in patients surviving an out-of-hospital cardiac arrest might significantly improve the rates of neurologically intact survivals on long term [2].
It has been proved that via application of therapeutic hypothermia protocols, a 7% reduction in cerebral metabolism can be achieved per each 1oC of hypothermia, that would further lead to a decrease consumption of glucose and oxygen and prevention of neuronal injury [2]. All these are strongly correlated with the evolution of the neurological status in the post-resuscitation period. [More]
Residual Curarization and Postoperative Respiratory Complications Following Laparoscopic Sleeve Gastrectomy. The Effect of Reversal Agents: Sugammadex vs. Neostigmine
Background: Incomplete muscle relaxant reversal or re-curarization may be associated with postoperative respiratory complications. In this retrospective study we compared the incidence of postoperative residual curarization and respiratory complications in association with the type of muscle relaxant reversal agent, sugammadex or neostigmine, in patients undergoing laparoscopic sleeve gastrectomy.
Material and methods: We reviewed the charts of all patients (179) undergoing laparoscopic sleeve gastrectomy from July 2012 to July 2013 at Wolfson Medical Center. Sugammadex 1.5-2 mg/kg (112 patients) or neostigmine 2.5 mg (67 patients) were used as reversal agents. Results were compared by the type of reversal agent employed. Compared parameters included demographic and anaesthetic data, residual curarization, oxyhemoglobin saturation (SpO2) in the recovery room (PACU), episodes of SpO2 lower than 90% in PACU, unexpected intensive care (ICU) admissions, incidence of atelectasis and pneumonia, re-intubation and duration of hospitalization.
Results: Obstructive sleep apnea syndrome (OSAS) was more frequent in the sugammadex group (19% vs. 8%; p = 0.026). Total intravenous anesthesia (TIVA) was more frequently associated with sugammadex (33% vs. 16%; p = 0.007). There were no differences in postoperative residual curarization, SpO2 < 90% episodes, reintubation, ICU admissions, pulmonary complications and duration of hospitalization.
Conclusion: With the inherent limitations of a retrospective study, the use of sugammadex following laparoscopic sleeve gastrectomy showed no advantage over neostigmine in terms of residual curarization and respiratory complications.
Differential Diagnosis and Management Issues of Idiopathic Angiooedema and their Resolution
Angiooedema is a local and self-limiting swelling of the subcutaneous and sub mucosal tissues, produced by vasoactive peptides that temporary increase the vascular permeability.
It is recognized that recurrent angiooedema exposes patients to the risk of fatalities and reduced quality of life, being in some circumstances associated with a critical condition.
Angiooedema can occur with or without wheals. The first symptom is urticaria, the second is a distinct nosologic entity. In absence of an identifiable cause, recurrent angiooedema without wheals can be defined as idiopathic and marked“idiopathic histaminergic angiooedema” when it is responsive to anti histamine treatment, and “idiopathic non-histaminergic angiooedema” when it is not. Furthermore, idiopathic non-histaminergic angiooedema can be diagnosed as hereditary or sporadic by family history.
In this review, we summarize the approaches to diagnose and treat different forms of idiopathic angiooedema.